Supramolecular polymeric vesicles are constructed by the complexation of p-sulfonatocalix[4]arene and chitosan, where the multivalent electrostatic interactions between the anionic sulfonate tetramer and cationic polyammoniums served as the dominant driving force. The supra-amphiphilic assemblies are disassembled upon exposure to a pH stimulus since the partial deprotonation of chitosan accompanied by a pH increase. Adding a competitive guest can also disrupt the assembly, representing the host-guest inclusion response. Interestingly, an abnormal temperature-response is observed, possibly as a result of the temperature-directed fusion process.

This paper reports the preparation and properties of color-switchable fluorescent carbon nanodots (C-dots). C-dots that emit dark turquoise and green-yellow fluorescence under 365 nm UV illumination were obtained from the hydrothermal decomposition of citric acid. Dark green fluorescent C-dots were obtained by conjugating prepared C-dots to form C-dot@C-dot nanoparticles. After successful conjugation of the C-dots, the fluorescence emission undergoes a blue shift of nearly 20 nm (?0.15 eV) under UV excitation at 370 nm. The C-dots emit golden rod, green-yellow, and gold light under excitation at 455 nm, which shows that the prepared C-dots are color-switchable. Furthermore, conjugation of the C-dots results in enhanced, red-shifted absorption of the ?-?* transition of the aromatic sp2 domains due to the conjugated ?-electron system. N incorporation in the carbon structure leads to a degree of dipoles for all the aromatic sp2 bonds. The enhanced absorption in a wide range from 226 to 601 nm indicates extended conjugation in the C-dot@C-dot structure. The time-resolved average lifetimes for the three different types of C-dots prepared in this study are 7.10, 7.65, and 4.07 ns. The radiative rate (reduced decay lifetime) increases when the C-dots are conjugated in the C-dot@C-dot nanoparticles, leading to the enhanced fluorescence emission. The fluorescence emission of the C-dot@C-dot nanoparticles can be used in applications such as flow cytometry and cell imaging.

Histone methylations have been implicated to play important roles in diverse cellular processes. Of particular interest is the methylation of histone H3K79, which is catalyzed by an evolutionarily conserved methyltransferase, disruptor of telomeric silencing (Dot1)-like (Dot1L). To investigate the role of Dot1L during vertebrate development, we have generated a Dot1L-specific transcription activator-like effector nuclease (TALEN) nuclease to knockdown endogenous Dot1L in Xenopus tropicalis, a diploid species highly related to the well-known developmental model Xenopus laevis, a pseudotetraploid amphibian. We show that the TALEN was extremely efficient in mutating Dot1L when expressed in fertilized eggs, creating essentially Dot1L knockout embryos with little H3K79 methylation. Importantly, we observed that Dot1L knockdown had no apparent effect on embryogenesis because normally feeding tadpoles were formed, consistent with the lack of maternal Dot1L expression. On the other hand, Dot1L knockdown severely retarded the growth of the tadpoles and led to tadpole lethality prior to metamorphosis. These findings suggest that Dot1L and H3K79 methylation play an important role for tadpole growth and development prior to metamorphosis into a frog. Our findings further reveal interesting similarities and differences between Xenopus and mouse development and suggest the existence of 2 separate phases of vertebrate development with distinct requirements for epigenetic modifications.-Wen, L., Fu, L., Guo, X., Chen, Y., Shi, Y.-B. Histone methyltransferase Dot1L plays a role in postembryonic development in Xenopus tropicalis.

A rapid and divergent access to chiral azacyclic nucleoside analogues has been established via highly exo-selective and enantioselective 1,3-dipolar cycloaddition of azomethine ylides with ?-nucleobase substituted acrylates. Using 1 mol% of a chiral copper complex, various chiral azacyclic nucleoside analogues were obtained in high yields, excellent exo-selectivities and enantioselectivities (98 to >99% ee).

The subsurface urban heat island (SubUHI) is one part of the overall UHI specifying the relative warmth of urban ground temperatures against the rural background. To combat the challenge on measuring extensive underground temperatures with in situ instruments, we utilized satellite-based moderate-resolution imaging spectroradiometer data to reconstruct the subsurface thermal field over the Beijing metropolis through a three-time-scale model. The results show the SubUHI's high spatial heterogeneity. Within the depths shallower than 0.5 m, the SubUHI dominates along the depth profiles and analyses imply the moments for the SubUHI intensity reaching first and second extremes during a diurnal temperature cycle are delayed about 3.25 and 1.97 h per 0.1 m, respectively. At depths shallower than 0.05 m in particular, there is a subsurface urban cool island (UCI) in spring daytime, mainly owing to the surface UCI that occurs in this period. At depths between 0.5 and 10 m, the time for the SubUHI intensity getting to its extremes during an annual temperature cycle is lagged 26.2 days per meter. Within these depths, the SubUHI prevails without exception, with an average intensity of 4.3 K, varying from 3.2 to 5.3 K.

Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor ?, IL-1?, and Th1-related cytokines IL-12 and IFN-?. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor ?t. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-? and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis.

The blood coagulation enzyme factor Xa (FXa) is a particularly promising target for anticoagulant therapy, and identification of oral small-molecule inhibitors of FXa remains a research focus. On the basis of the X-ray crystal structure of FXa and its inhibitor rivaroxaban, we designed and synthesized a series of conformationally restricted mimics containing a novel [6,6,5] tricyclic fused oxazolidinone scaffold. Intensive structure-activity relationship (SAR) and structure-pharmacokinetic relationship (SPR) studies on this new series led to the discovery of compound 11a: a highly potent, selective, direct, and orally bioavailable FXa inhibitor with excellent in vivo antithrombotic efficacy and preferable pharmacokinetic profiles. Druggability evaluation of compound 11a was undertaken and elicited positive outcomes. All results indicate that compound 11a is a promising drug candidate for the prevention and treatment of thromboembolic diseases in venous and arterial systems.

In previous reports concerning the association between sex disparity and age, gastric cancer (GC) patients were simply divided into younger and older groups by age. We analyzed the age trend of the male to female sex ratio (MFSR) in GC based on patient sequential age in order to observe the changing process of MFSR with age.

With a ruthenium-porphyrin catalyst, alkyl diazomethanes generated in situ from N-tosylhydrazones efficiently underwent intramolecular C(sp(3) )?H insertion of an alkyl carbene to give substituted tetrahydrofurans and pyrrolidines in up to 99?% yield and with up to 99:1 cis selectivity. The reaction displays good tolerance of many functionalities, and the procedure is simple without the need for slow addition with a syringe pump. From a synthetic point of view, the C?H insertion of N-tosylhydrazones can be viewed as reductive coupling between a C?O bond and a C?H bond to form a new C?C bond, since N-tosylhydrazones can be readily prepared from carbonyl compounds. This reaction was successfully applied in a concise synthesis of (+)-pseudoheliotridane.

A plasmonic mode-selection filter based on end-coupled circular split-ring resonators is proposed and demonstrated. In contrast to regular ring resonators, which can support only the integer modes, extra noninteger resonance modes will be excited by placing metallic nanowalls in the proposed circular ring resonators. Since all the modes are highly sensitive to the position of the nanowall, the associated modes are effectively excited or suppressed by manipulating the position. This proposed scheme offers great flexibility to design the transmission spectrum with expected modes. Moreover, each integer or noninteger resonance mode with high transmittance can be selected individually by cascading two proposed split-ring resonators that share an intersection of transmission peaks. The corresponding spectra and the propagation characteristics are numerically investigated by using the finite-difference time-domain method.

We demonstrate the coating of various 2D nanomaterials including MoS2 nanosheets, graphene oxide (GO), and reduced graphene oxide (rGO) with zeolitic imidazolate frameworks (i.e., ZIF-8) via a facile procedure. Additionally, ternary core-shell structures like Pt-MoS2@ZIF-8, Pt-GO@ZIF-8, and Pt-rGO@ZIF-8 have also been prepared. As a proof-of-concept application, a memory device based on MoS2@ZIF-8 hybrid was fabricated and it exhibited write-once-read-many-times (WORM) memory effect with high ON/OFF ratio and long operating lifetime. It is expected that MOF coated 2D nanomaterials may find wide applications in energy storage and conversion, catalysis, sensing, and information storage devices.

Ying-zhi-huang injection (YZH-I) is an injectable multi-herbal prescription derived from the ancient Chinese remedy "Yin-chen-hao-tang", which is widely used in the clinic for the treatment of jaundice and chronic liver diseases. To date, little information is available on the pharmacokinetic properties of this poly-herbal formulation. Herein, we reported a simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitative multiple reaction monitoring (MRM) of eight major ingredients of YZH-I (including baicalin, baicalein, wogonoside, geniposide, geniposidic acid, chlorogenic acid, neochlorogenic acid, and caffeic acid) in rat plasma. A fast single-tube multi-impurity precipitation extraction ("SMIPE") procedure was introduced for straightforward plasma preparation, based on one-pot deproteinization precipitation with acidified methanol extraction and in-situ multifunction impurity removal by a solid sorbent mixture (anh. magnesium sulfate plus octadecylsilane). Particularly, the addition of ascorbic acid in methanol (10 mg/mL) was found to exhibit a pronounced protective effect and significantly increase extraction effectiveness of the herbal phenolic components. Some pretreatment variables (protein precipitating solvent, acidifying agent and sorbent) were optimized with acceptable matrix effect (-18 to 7.7%), extraction recovery (65-88%) and process efficiency (62-91%) for the SMIPE-based LC-MRM multi-analyte quantitation using matrix-matched calibration (5-1000 ng/mL) without using internal standard. Mean accuracies were obtained in the range of 83-114% at three different fortification levels, with intra- and inter-day variations within 13%. This validated method was successfully applied to the simultaneous measurement and pharmacokinetic investigation of the chemical constituents in rats following an intravenous administration of YZH-I.

Ido2 is involved in tryptophan catabolism and immunity, but its physiological functions remain poorly understood. This study was undertaken to examine the expression and regulation of Ido2 gene in mouse uterus during the peri-implantation period. The results showed that Ido2 mRNA was highly expressed on day 4 of pregnancy and in the delayed implantation uterus. On days 5-8 of pregnancy, a low level of Ido2 expression was observed in the uteri. Simultaneously, Ido2 mRNA was also lowly expressed in the decidualized uterus. In the uterine stromal cells, 8-Br-cAMP could inhibit the expression of Ido2 mRNA. Moreover, Ido2 mRNA expression was gradually decreased after the stromal cells were treated with estrogen and progesterone and reached a nadir at 96 h. Further study found that overexpression of Ido2 could downregulate the expression of decidualization marker genes PRL, IGFBP1, and Dtprp under in vitro decidualization, while inhibition of Ido2 with devo-1-methyl-tryptophan (D-1-MT) could upregulate the expression of these marker genes. Under in vitro decidualization, overexpression of Ido2 could suppress the proliferation of uterine stromal cells and elevate the expression of Bax and MMP2 genes. On the contrary, Ido2 inhibitor D-1-MT could enhance the proliferation of stromal cells and expression of Bcl2 gene but decline the Bax/Bcl2 ratio. In the uterine stromal cells, estrogen and progesterone could induce the expression of Ido2 mRNA. These data indicate that Ido2 may be important for mouse embryo implantation and decidualization.

A novel method of fabricating large-scale horizontally aligned ZnO microrod arrays with controlled orientation and periodic distribution via combing technology is introduced. Horizontally aligned ZnO microrod arrays with uniform orientation and periodic distribution can be realized based on the conventional bottom-up method prepared vertically aligned ZnO microrod matrix via the combing method. When the combing parameters are changed, the orientation of horizontally aligned ZnO microrod arrays can be adjusted (? = 90° or 45°) in a plane and a misalignment angle of the microrods (0.3° to 2.3°) with low-growth density can be obtained. To explore the potential applications based on the vertically and horizontally aligned ZnO microrods on p-GaN layer, piezo-phototronic devices such as heterojunction LEDs are built. Electroluminescence (EL) emission patterns can be adjusted for the vertically and horizontally aligned ZnO microrods/p-GaN heterojunction LEDs by applying forward bias. Moreover, the emission color from UV-blue to yellow-green can be tuned by investigating the piezoelectric properties of the materials. The EL emission mechanisms of the LEDs are discussed in terms of band diagrams of the heterojunctions and carrier recombination processes.

The ribosome-associated nascent polypeptide-associated complex (NAC) is involved in multiple cotranslational processes, including protein transport into the ER and mitochondria, and also acts as a chaperone to assist protein folding. Here we demonstrated that NAC is also essential for autophagic degradation of a variety of protein aggregates in C. elegans. Loss of function of NAC impairs lysosome function, resulting in accumulation of autophagic substrates in enlarged autolysosomes. Knockdown of mammalian NAC also causes accumulation of nondegradative autolysosomes. Our study revealed that NAC plays an evolutionarily conserved role in the autophagy pathway and thus in maintaining protein homeostasis under physiological conditions.

Mesenteric fat plays an important role in the pathogenesis of Crohn's disease (CD), and a higher ratio of visceral fat area (VFA) to subcutaneous fat area (SFA) is related to complicated disease status. Exclusive enteral nutrition (EEN) is an effective treatment option for patients with CD, and the aims of this study were to assess the effects of EEN on abdominal fat in patients with CD.

Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research.

Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.

It has been considered that cesarean delivery is a risk factor for the two subtypes of inflammatory bowel diseases (IBDs): Crohn's disease (CD) and ulcerative colitis (UC). The aim of this meta-analysis was to examine the relationship between cesarean delivery and the development of IBD.

Pancreatic cancer is one of the most aggressive solid malignancies with a dismal survival rate. Recent studies have shown that high expression levels of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) correlate with several solid tumors. However, the underlying molecular mechanisms and its clinical significance in pancreatic cancer remain to be elucidated. In the present study, our results showed that MALAT-1 expression levels were upregulated in pancreatic cancer tissues compared with adjacent noncancerous controls. Consistently, higher expression level of MALAT-1 was found in all seven pancreatic cancer cell lines relative to the human pancreatic ductal epithelial cell. Further function analysis revealed that downregulation of MALAT-1 could inhibit tumor cell proliferation and decrease cell migration and invasion in vitro. The underlying mechanisms are possibly involved in inducing G2/M cell cycle arrest, promoting cell apoptosis, suppressing epithelial-mesenchymal transition and reducing cancer stem-like properties. In conclusion, this study indicated that MALAT-1 may serve as an oncogenic lncRNA that is involved in malignancy phenotypes of pancreatic cancer. Therefore, it may be used as a potential therapeutic target.

MicroRNAs (miRNAs) play an important role in inflammation. Several studies have reported the unique miRNAs profiles in colonic mucosa and peripheral blood of patients with active Crohn's disease (CD). But there is limited data about the miRNA profiles of terminal ileum, the most commonly involved location, especially the non-inflamed mucosa. We aimed to investigate the miRNAs expression of both inflamed and non-inflamed terminal ileal mucosa in adult patients with active CD.

Pancreatic cancer is one of the most aggressive solid malignancies with a dismal survival rate. Recent studies have shown that high expression levels of histone deacetylase 3 (HDAC3) correlate with malignant phenotype. However, the expression patterns and biological role of HDAC3 in pancreatic cancer remain unclear. In this study, our data showed that a higher level of HDAC3 protein expression was found in pancreatic cancer as compared to paired paracancerous tissues. Consistently, higher expression level of HDAC3 was found in all of the eight pancreatic cancer cell lines relative to human pancreatic ductal epithelial cells (HPDE). In addition, further function analysis revealed that HDAC3 can function as oncogenic protein, which could promote pancreatic cancer cell proliferation, migration and invasion, and may increase drug resistance. Moreover, the functional involvement of HDAC3 was partially correlated with post-induction repression of P53, P27 and Bax gene transcription, acting via H3K9 deacetylation. Taken together, our data suggest that HDAC3 participates in the pathogenesis and progression of pancreatic cancer through histone modification, which might be a pivotal epigenetic target against this devastating disease.

Measurements of body composition by dual-energy X-ray absorptiometry (DXA) have evident value in evaluating skeletal and muscular status in growing children and adolescents. This study aimed to generate age-related trends for body composition in Chinese children and adolescents, and to establish gender-specific reference percentile curves for the assessment of muscle-bone status. A total of 1541 Chinese children and adolescents aged from 5 to 19 years were recruited from southern China. Bone mineral content (BMC), lean mass (LM) and fat mass (FM) were measured for total body and total body less head (TBLH). After 14 years, total body LM was significantly higher in boys than girls (p

Abstract Background: The chronic use of the long-acting anticholinergic agent, tiotropium, in chronic obstructive pulmonary disease (COPD) has been linked in some reports to an increase in adverse cardiovascular effects. Decreased heart rate variability (HRV) is a condition seen in COPD patients that has also been linked to poor cardiovascular outcome. We aimed in this study to investigate changes in HRV caused by tiotropium administration to COPD patients in order to determine whether changes occurred that might contribute to an increase in adverse cardiovascular events. Methods: Seventy patients with moderate-to-severe stable COPD were treated with once-daily dosing of tiotropium (two puffs of Spiriva Respimat, 2.5??g solution) for 3 months. HRV, pulmonary function, and quality of life were measured before and after 1 and 3 months of therapy. Results: Pulmonary function and quality of life improved significantly, after both 1 and 3 months of therapy. No significant change in HRV parameters occurred, except for a significant decrease in the high-frequency and increase in the low-frequency component of HRV at the 1-month assessment. Conclusion: Changes in HRV caused by tiotropium use are not sufficient to explain a possible increase in adverse cardiovascular events.

Entosis, a cell-in-cell process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TIP150 facilitates the loading of MCAK onto the microtubule plus ends and orchestrates microtubule plus-end dynamics during cell division. Here we show that TIP150 cooperates with MCAK to govern entosis via a regulatory circuitry that involves Aurora A-mediated phosphorylation of MCAK. Our biochemical analyses show that MCAK forms an intra-molecular association, which is essential for TIP150 binding. Interestingly, Aurora A-mediated phosphorylation of MCAK modulates its intra-molecular association, which perturbs the MCAK-TIP150 interaction in vitro and inhibits entosis in vivo. To probe if MCAK-TIP150 interaction regulates microtubule plasticity to affect the mechanical properties of cells during entosis, we used an optical trap to measure the mechanical rigidity of live MCF7 cells. We find that the MCAK cooperates with TIP150 to promote microtubule dynamics and modulate the mechanical rigidity of the cells during entosis. Our results show that a dynamic interaction of MCAK-TIP150 orchestrated by Aurora A-mediated phosphorylation governs entosis via regulating microtubule plus-end dynamics and cell rigidity. These data reveal a previously unknown mechanism of Aurora A regulation in the control of microtubule plasticity during cell-in-cell processes.

Sexual dimorphism does occur in intervertebral disc (IVD) degeneration. The involvement of estrogen on IVD health has been well reported in recent years. The estrogen receptors (ER) are the main mediators of estrogen action. ER might play specific roles in the sexual variations of the IVD degeneration.

To report operative and long-term results after surgery for chronic radiation enteritis and to evaluate the therapeutic efficacy of surgery and investigate the risk factors of postoperative survival rate.

Overdose of acetaminophen (APAP) can cause acute liver injury that is sometimes fatal, requiring efficient pharmacological intervention. The traditional Chinese herb Bupleurum falcatum has been widely used for the treatment of several liver diseases in eastern Asian countries, and saikosaponin d (SSd) is one of its major pharmacologically-active components. However, the efficacy of Bupleurum falcatum or SSd on APAP toxicity remains unclear. C57/BL6 mice were administered SSd intraperitoneally once daily for 5days, followed by APAP challenge. Biochemical and pathological analysis revealed that mice treated with SSd were protected against APAP-induced hepatotoxicity. SSd markedly suppressed phosphorylation of nuclear factor kappa B (NF-?B) and signal transducer and activator of transcription 3 (STAT3) and reversed the APAP-induced increases in the target genes of NF-?B, such as pro-inflammatory cytokine Il6 and Ccl2, and those of STAT3, such as Socs3, Fga, Fgb and Fgg. SSd also enhanced the expression of the anti-inflammatory cytokine Il10 mRNA. Collectively, these results demonstrate that SSd protects mice from APAP-induced hepatotoxicity mainly through down-regulating NF-?B- and STAT3-mediated inflammatory signaling. This study unveils one of the possible mechanisms of hepatoprotection caused by Bupleurum falcatum and/or SSd.

Human induced pluripotent stem cells (iPSC) can be used to understand the pathological mechanisms of human disease. These cells are a promising source for cell-replacement therapy. However, such studies require genetically defined conditions. Such genetic manipulations can be performed using the novel Transcription Activator-Like Effector Nucleases (TALENs), which generate site-specific double-strand DNA breaks (DSBs) with high efficiency and precision. Combining the TALEN and iPSC methods, we developed two iPS cell lines by generating the point mutation A5768G in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 ? subunit. The engineered iPSC maintained pluripotency and successfully differentiated into neurons with normal functional characteristics. The two cell lines differ exclusively at the epilepsy-susceptibility variant. The ability to robustly introduce disease-causing point mutations in normal hiPS cell lines can be used to generate a human cell model for studying epileptic mechanisms and for drug screening.

CONSPECTUS: Developments in macrocyclic chemistry have led to supramolecular chemistry, a field that has attracted increasing attention among researchers in various disciplines. Notably, the discoveries of new types of macrocyclic hosts have served as important milestones in the field. Researchers have explored the supramolecular chemistry of several classical macrocyclic hosts, including crown ethers, cyclodextrins, calixarenes, and cucurbiturils. Calixarenes represent a third generation of supramolecular hosts after cyclodextrins and crown ethers. Easily modified, these macrocycles show great potential as simple scaffolds to build podand-like receptors. However, the inclusion properties of the cavities of unmodified calixarenes are not as good as those of other common macrocycles. Calixarenes require extensive chemical modifications to achieve efficient endo-complexation. p-Sulfonatocalix[n]arenes (SCnAs, n = 4-8) are a family of water-soluble calixarene derivatives that in aqueous media bind to guest molecules in their cavities. Their cavities are three-dimensional and ?-electron-rich with multiple sulfonate groups, which endow them with fascinating affinities and selectivities, especially toward organic cations. They also can serve as scaffolds for functional, responsive host-guest systems. Moreover, SCnAs are biocompatible, which makes them potentially useful for diverse life sciences and pharmaceutical applications. In this Account, we summarize recent work on the recognition and assembly properties unique to SCnAs and their potential biological applications, by our group and by other laboratories. Initially examining simple host-guest systems, we describe the development of a series of functional host-guest pairs based on the molecular recognition between SCnAs and guest molecules. Such pairs can be used for fluorescent sensing systems, enzymatic activity assays, and pesticide detoxification. Although most macrocyclic hosts prevent self-aggregation of guest molecules, SCnAs can induce self-aggregation. Researchers have exploited calixarene-induced aggregation to construct supramolecular binary vesicles. These vesicles respond to internal and external stimuli, including temperature changes, redox reactions, additives, and enzymatic reactions. Such structures could be used as drug delivery vehicles. Although several biological applications of SCnAs have been reported, this field is still in its infancy. Continued exploration of the supramolecular chemistry of SCnAs will not only improve the existing biological functions but also open new avenues for the use of SCnAs in the fields of biology, biotechnology, and pharmaceutical research. In addition, we expect that other interdisciplinary research efforts will accelerate developments in the supramolecular chemistry of SCnAs.

We report here a supramolecular strategy to directly assemble the small molecular antipsychotic drug chlorpromazine (CPZ) into nanostructures, induced by p-sulfonatocalix[4]arene (SC4A) and p-sulfonatocalix[4]arene tetraheptyl ether (SC4AH), with high drug loading efficiencies of 61% and 46%, respectively. The binary host-guest assembly process was monitored using optical transmittance measurements, and the size and morphology of these two kinds of supra-amphiphilic assemblies were identified using a combination of light scattering and high-resolution transmission electron microscopy, which showed solid spherical micelles. This strategy presents new opportunities for the development of high loading drug-containing carriers with easy processability for drug delivery.

Enzyme-responsive assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites at which the target enzymes are located. In this work, based on the concept of host-guest chemistry, a trypsin-responsive supramolecular vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural serine protease trypsin-cleavable cationic protein protamine as the guest molecule, is reported. The complexation of p-sulfonatocalix[4]arene with protamine directs the formation of a supramolecular binary vesicle, which is dissipated by trypsin with high selectivity. Therefore, the present system represents a principle-of-concept to build a controlled-release carrier at trypsin-overexpressed sites.

We present a facile method for fabricating spongelike Au structures by halide-induced aggregation and fusion of gold nanoparticles (AuNPs). Halide ions (F(-), Cl(-), Br(-), and I(-)) showed distinctly different effects on the synthesized AuNPs, which were characterized by localized surface plasmon resonance (LSPR) and dynamic light scattering measurements. A noticeable red-shift in the LSPR peak was found after Br(-) and I(-) ion treatment, which indicates the adsorption of halide atoms or ions on the AuNPs. The surface potential of AuNPs varied by treatment with different types of halides; this finding indicates that different halide ions have different effects on the AuNPs. Br(-) and I(-) ions showed strong affinity toward the AuNPs. The different affinities of halide ions toward the AuNPs play an important role in controlling the formation process of spongelike gold. Citrate ions adsorbed on AuNPs were displaced by halide ions to different extents. Such displacement determined the aggregation and fusion behaviors of the AuNPs and eventually the formation of different spongelike structures.

A water-soluble supramolecular polymer with a high degree of polymerization and viscosity has been constructed based on the strong host-guest interaction between p-sulfonatocalix[4]arenes (SC4As) and viologen. A homoditopic doubly ethyl-bridged bis(p-sulfonatocalix[4]arene) (d-SC4A) was prepared and its binding behavior towards methyl viologen compared with the singly ethyl-bridged bis(p-sulfonatocalix[4]arene) (s-SC4A) by NMR spectroscopy and isothermal titration calorimetry. By employing a viologen dimer (bisMV(4+)) as the homoditopic guest, two linear AA/BB-type supramolecular polymers, d-SC4A?bisMV(4+) and s-SC4A?bisMV(4+), were successfully constructed. Compared with s-SC4A?bisMV(4+), d-SC4A?bisMV(4+) shows much higher solubility and viscosity, and has also been characterized by viscosity, diffusion-ordered NMR spectroscopy, dynamic light scattering, and atomic force microscopy measurements. Furthermore, the polymer is responsive to electrostimulus as viologen is electroactive, which was studied by cyclic voltammetry. This study represents a proof-of-principle as the polymer can potentially be applied as a self-healing and degradable polymeric material.

Mesenteric hypertrophy has been recognised as an indicator of the complicated course of Crohn's disease. The aim of this study was to investigate whether the visceral fat area (VFA) was associated with postoperative clinical and endoscopic recurrence.

Artemisinin (ART) is an iron-dependent anti-cancer drug. However, simultaneous delivery of hydrophobic ART and Fe(2+) ions into cancer cells remains a major challenge. Herein, we reported Fe3O4@C/Ag@mSiO2 (FCA@mSiO2) multifunctional nanocarriers which can load ART as high as 484 mg/g. Moreover, FCA@mSiO2 nanoparticles demonstrated pH-responsive Fe(2+) release, the concentration of Fe(2+) ions can reach 2.765 nmol/L in HeLa cells cultured with FCA@mSiO2 nanoparticles. The antitumor efficacy of ART-loaded FCA@mSiO2 nanoparticles measured by MTT assay was significantly enhanced compared with free ART. It was suggested that the ART-loaded FCA@mSiO2 nanoparticles are internalized by HeLa cells and located at the acidic compartments of endosomes and lysosomes, releasing Fe(2+) ions to non-enzymatically convert ART to toxic products for killing cancer cells. This result provides a way for using promising natural drugs in anti-cancer therapeutics.

Oxidation catalysis not only plays a crucial role in the current chemical industry for the production of key intermediates such as alcohols, epoxides, aldehydes, ketones and organic acids, but also will contribute to the establishment of novel green and sustainable chemical processes. This review is devoted to dealing with selective oxidation reactions, which are important from the viewpoint of green and sustainable chemistry and still remain challenging. Actually, some well-known highly challenging chemical reactions involve selective oxidation reactions, such as the selective oxidation of methane by oxygen. On the other hand some important oxidation reactions, such as the aerobic oxidation of alcohols in the liquid phase and the preferential oxidation of carbon monoxide in hydrogen, have attracted much attention in recent years because of their high significance in green or energy chemistry. This article summarizes recent advances in the development of new catalytic materials or novel catalytic systems for these challenging oxidation reactions. A deep scientific understanding of the mechanisms, active species and active structures for these systems are also discussed. Furthermore, connections among these distinct catalytic oxidation systems are highlighted, to gain insight for the breakthrough in rational design of efficient catalytic systems for challenging oxidation reactions.

We retrospectively compared the clinical outcomes of autogenous coronoid process grafts (n=32) and costochondral grafts (n=28) in condylar reconstruction for the treatment of unilateral ankylosis of the temporomandibular joint (TMJ) in adults. Preoperative and postoperative assessments included diet scores, cone-beam computed tomography (CT), maximal interincisal opening, lateral excursion, and mandibular deviation on opening the mouth. There were no significant differences between the 2 groups in the measurements before and after the operation with respect to incisal opening, lateral excursion, mandibular deviation, diet scores, or recurrence rate, but in both the postoperative incisal opening, lateral excursion, and diet scores had improved significantly compared with preoperatively. After costochondral graft 3 patients developed intraoperative plural tears, and 6 had temporary pain at the donor site. The frontal branch of the facial nerve was temporarily affected in 5 patients after costochondral graft and 3 after coronoid process grafts, all of which recovered in 3-6 months. There was no recurrence after coronoid process grafting, and one after costochondral grafting. The clinical outcomes in both groups were satisfactory and comparable. Autogenous coronoid process grafting may therefore be a good alternative for condylar reconstruction in patients with ankylosis of the TMJ.

Rainfall anomalies over southern China are found to be asymmetricly influenced by the Indian Ocean Dipole (IOD), with a far stronger influence from positive IOD (pIOD) events. A greater convection anomaly and an equivalent-barotropic Rossby wave train response occurs during pIOD events than during negative IOD (nIOD) events. Over the Bay of Bengal (BOB) and South China Sea (SCS), an associated low-level anomalous anticyclone strengthens the southwesterlies during boreal fall (September, October and November, SON), when a pIOD matures. The increased moisture flux gives rise to the anomalously high rainfall over southern China. During its developing phase (boreal summer, June, July, and August, JJA), the influence of a pIOD event on the contemporaneous rainfall over southern China is weak, but a JJA pIOD index is highly correlated with fall rainfall. Therefore, this index can serve as a potential predictor for variations of boreal fall rainfall over southern China.

Self-assembled fluorescent nanoparticles responding to specific stimuli are highly appealing for applications such as labels, probes, memory devices, and logic gates. However, organic analogues are challenging to prepare, due to unfavorable aggregation-caused quenching. We herein report the preparation of self-assembled fluorescent organic nanoparticles in water by means of calixarene-induced aggregation of a tetraphenylethene derivative (QA-TPE) mediated by p-sulfonatocalix[4]arenes. The self-assembled nanoparticles showed interesting photoswitching behaviors, and the fluorescence output of the generated nanoparticles was opposite to that of free QA-TPE both before and after irradiation. Free QA-TPE is nonfluorescent, owing to intramolecular rotations of the phenyl rings. In contrast, the self-assembled nanoparticles that formed upon complexation of QA-TPE with p-sulfonatocalix[4]arene exhibited aggregation-induced emission fluorescence (?(em) = 480 nm, ? = 14%), as a result of the inhibition of rotations. Upon UV light irradiation, free QA-TPE was cyclized to the corresponding diphenylphenanthrene, which showed typical fluorescence of a ?-conjugated system (?(em) = 385 nm, ? = 9.3%), whereas the nanoparticles were nonfluorescent upon irradiation due to the aggregation-caused quenching. In effect, this system allows programmed modulation of TPE fluorescence at two different emission wavelengths by means of host-guest complexation and irradiation. Relative to a single-mode stimulus-responsive system, our new developed system of highly integrated modes into a single molecular unit that can exhibit modulation of fluorescence by multiple stimulus is expected to be more adaptable for practical applications and to show enhanced multifunctionality.

Checkpoint kinase 1 (CHEK1) is an evolutionarily conserved Ser/Thr kinase, which mediates cell-cycle arrest after DNA damage, and we previously reported that CHEK1 was overexpressed and associated with poor prognosis in hepatocellular carcinoma (HCC), indicating it was oncogenic gene. In this study, we aimed to elucidate the mechanism of CHEK1 overexpression in HCC. We first verified the upregulated CHEK1 by qRT-PCR and western blot in 30 HCC samples compared with corresponding non-tumor liver tissues. In silico analysis showed that CHEK1 was a candidate target of miR-497, which was previously found to be downregulated in HCC by us. To test whether miR-497 could bind to 3'untranslated region (3'UTR) of CHEK1, luciferase reporter assay was conducted. The result revealed that miR-497 could bind to the 3'untranslated region (3'UTR) of CHEK1 mRNA. Western blot showed that ectopic expression of miR-497 suppressed the CHEK1 expression and inhibition of miR-497 led to significant upregulation of CHEK1. Finally, miR-497 expression was measured in the same 30 HCC samples, and the correlation between miR-497 and CHEK1 was analyzed. The results indicated that miR-497 was downregulated in HCC and had a significant negative correlation with CHEK1. Taken together, these results demonstrated that CHEK1 was negatively regulated by miR-497, and the overexpressed CHEK1 was resulted from the downregulated miR-497 in HCC, which provided a potential molecular target for HCC therapy.

The high-mobility group protein (HMO2) of Saccharomyces cerevisiae is a component of the chromatin-remodelling complex INO80, which is involved in double-strand break (DSB) repair. HMO2 can also bind DNA to protect it from exonucleolytic cleavage. Nevertheless, little structural information is available regarding these functions of HMO2. Since determination of three-dimensional structure is a powerful means to facilitate functional characterization, X-ray crystallography has been used to accomplish this task. Here, the expression, purification, crystallization and preliminary crystallographic analysis of HMO2 from S. cerevisiae are reported. The crystal belonged to space group P222, with unit-cell parameters a = 39.35, b = 75.69, c = 108.03?Å, and diffracted to a resolution of 3.0?Å. The crystals are most likely to contain one molecule in the asymmetric unit, with a VM value of 3.19?Å(3)?Da(-1).

For the emerging amphibian genetic model Xenopus tropicalis targeted gene disruption is dependent on zinc-finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), which require either complex design and selection or laborious construction. Thus, easy and efficient genome editing tools are still highly desirable for this species. Here, we report that RNA-guided Cas9 nuclease resulted in precise targeted gene disruption in all ten X. tropicalis genes that we analyzed, with efficiencies above 45% and readily up to 100%. Systematic point mutation analyses in two loci revealed that perfect matches between the spacer and the protospacer sequences proximal to the protospacer adjacent motif (PAM) were essential for Cas9 to cleave the target sites in the X. tropicalis genome. Further study showed that the Cas9 system could serve as an efficient tool for multiplexed genome engineering in Xenopus embryos. Analysis of the disruption of two genes, ptf1a/p48 and tyrosinase, indicated that Cas9-mediated gene targeting can facilitate direct phenotypic assessment in X. tropicalis embryos. Finally, five founder frogs from targeting of either elastase-T1, elastase-T2 or tyrosinase showed highly efficient transmission of targeted mutations into F1 embryos. Together, our data demonstrate that the Cas9 system is an easy, efficient and reliable tool for multiplex genome editing in X. tropicalis.

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platforms contributing to redefine the boundaries of modern biological research. They are composed of a non-specific cleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications by inducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases have been employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively. This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies, biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbits using transcription activator-like effector nucleases, and a perspective of the field.

Aberrant expression of histone deacetylase (HDACs) was associated with carcinogenesis and progression of various tumors. However, the association of HDAC10 with clinical outcomes in gastric cancer patients is unclear. Thus, the objective of the current study was to evaluate the association of expression level of HDAC10 with clinicopathologic factors and prognosis of patients with gastric cancer. The expression level of HDAC10 in 179 paraffin-embedded gastric cancer tissue specimens was examined by immunohistochemistry (IHC). As a result, we found that expression of HDAC10 in gastric cancer was significantly decreased in gastric cancer tissues as compared with adjacent tissues (51.4% vs. 87.3%, P < 0.001). HDAC10 expression was significantly correlated with gender (P = 0.023), tumor size (P = 0.015), histological grade (P = 0.009), tumor invasion (P = 0.033), lymph node metastatic status (P = 0.019) and tumor stage (P = 0.004), but not correlated with age and lauren classification (all P > 0.05). Kaplan-Meier survival curves showed that the overall survival rate was significantly lower in the patients with low expression of HDAC10 compared with those patients with high HDAC10 (P < 0.001). Moreover, multivariate analysis revealed that HDAC10 expression was an independent prognostic factor for gastric cancer patients (P = 0.001). These results suggest that HDAC10 expression could see as a prognosis marker for gastric cancer patients.

Abnormal expression of micro-ribonucleic acid (miRNA [miR])-128 has been observed in various human cancer types, and its validated target genes are implicated in cancer-related cellular processes, such as cell proliferation, differentiation, and apoptosis. Especially, it has been demonstrated that miR-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting PTEN, which functions as a tumor suppressor in this malignancy. In the current study, we investigated the involvement of miR-128 and its target gene PTEN in tumor progression and prognosis in patients with primary osteosarcoma.

Primary cutaneous ??-T-cell lymphoma (CGD-TCL) is a distinct disease entity which is an extremely rare neoplasm with poor prognosis, characterized by the ?/? T-cell receptor expression on atypical lymphocytes. We report the case of a 42-year-old man who first presented with a swelling in the extremities and subsequent appeared subcutaneous nodule over the body. In order to clarify the diagnosis, a biopsy of subcutaneous nodule for pathology had been done. CGD-TCL was diagnosed by histopathology, immunophenotype, in situ hybridization and analysis of TCR? genes rearrangement. The patient was treated with chemotherapeutic regimens-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone). After one period of chemotherapy, subcutaneous nodules became small, even disappeared, swelling and ulcer in the left pedal gone away gradually. One month later after first chemotherapy, tumor relapsed with lesions growing back rapidly, also showed disease in double lungs. The patient was just 10-month survival time from the onset. To our knowledge, this case is the first report of CGD-TCL with unilateral lower extremity swelling as the first-onset symptom. If patient is presented the first symptoms such as swelling of extremities, especially when ulceration appears, it is of great significance to be considerate about the possibility of CGD-TCL.

To review the cannulation strategies and associated vascular complications of extracorporeal membrane oxygenation (ECMO) and to investigate the etiology and preventive procedures for those complications.

China is and will be characterized by a large number of men who are unable to marry: these men are often referred to as "bare branches." In this paper we define the bare branch family and divide its life cycle into three stages: the unmarried co-resident with both parents, co-resident with a surviving parent, and living alone. Using life tables and probability methods, we find that up to age 60, the bare branch male faces cumulative probabilities of 0.8 and 0.6, for his fathers and mothers death, respectively. The definition of the age at which bare branch status is initialized influences the length of these stages. As the childbearing age of parents increases, the age of a bare branch at the death of his parents decreases, and the duration of his living alone lengthens. An increase in the mothers childbearing age, holding that of the father constant, shortens the stage of co-residence with both parents, and lengthens the stage of living alone.

In this paper, chloramphenicol was selected as a model drug to prepare in situ gels. The intrinsic dissolution rate of chloramphenicol from in situ gel was evaluated using the surface dissolution imaging system. The results indicated that intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel decreased significantly when the poloxamer concentration increased. The addition of the thickener reduced the intrinsic dissolution rate of chloramphenicol thermosensitive gel, wherein carbomer had the most impact. Different dilution ratios of simulated tear fluid greatly affected gel temperature, and had little influence on the intrinsic dissolution rate of chloramphenicol from the thermosensitive in situ gel. The pH of simulated tear fluid had little influence on the intrinsic dissolution rate of chloramphenicol thermosensitive in situ gel. For the pH sensitive in situ gel, the dissolution rates of chloramphenicol in weak acidic and neutral simulated tear fluids were slower than that in weak alkaline simulated tear fluid. In conclusion, the intrinsic dissolution of chloramphenicol from in situ gel was dependent on formulation and physiological factors. With advantages of small volume sample required and rapid detection, the UV imaging method can be an efficient tool for the evaluation of drug release characteristics of ophthalmic in situ gel.

Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dIL(A), and dIL(B) subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dIL(B) cells. In these CKO mice, development of a subset of excitatory neurons located in laminae I and II was impaired, including itch-related GRPR-expressing neurons, PKC?-expressing neurons, and neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1, and the gastrin-releasing peptide. These CKO mice displayed marked deficits in generating nocifensive motor behaviors evoked by a range of pain-related or itch-related stimuli. The mutants also failed to exhibit escape response evoked by dynamic mechanical stimuli but retained the ability to sense innocuous cooling and/or warm. Thus, our studies provide new insight into the ontogeny of spinal neurons processing distinct sensory modalities.

PKA signaling is important for the post-translational modification of proteins, especially those in cardiomyocytes involved in cardiac excitation-contraction coupling. PKA activity is spatially and temporally regulated through compartmentalization by protein kinase A anchoring proteins. Cypher/ZASP, a member of PDZ-LIM domain protein family, is a cytoskeletal protein that forms multiprotein complexes at sarcomeric Z-lines. It has been demonstrated that Cypher/ZASP plays a pivotal structural role in the structural integrity of sarcomeres, and several of its mutations are associated with myopathies including dilated cardiomyopathy. Here we show that Cypher/ZASP, interacting specifically with the type II regulatory subunit RII? of PKA, acted as a typical protein kinase A anchoring protein in cardiomyocytes. In addition, we show that Cypher/ZASP itself was phosphorylated at Ser(265) and Ser(296) by PKA. Furthermore, the PDZ domain of Cypher/ZASP interacted with the L-type calcium channel through its C-terminal PDZ binding motif. Expression of Cypher/ZASP facilitated PKA-mediated phosphorylation of the L-type calcium channel in vitro. Additionally, the phosphorylation of the L-type calcium channel at Ser(1928) induced by isoproterenol was impaired in neonatal Cypher/ZASP-null cardiomyocytes. Moreover, Cypher/ZASP interacted with the Ser/Thr phosphatase calcineurin, which is a phosphatase for the L-type calcium channel. Taken together, our data strongly suggest that Cypher/ZASP not only plays a structural role for the sarcomeric integrity, but is also an important sarcomeric signaling scaffold in regulating the phosphorylation of channels or contractile proteins.

Lipocalin ?1-microglobulin (?1M) is a conserved glycoprotein present in plasma and in the interstitial fluids of all tissues. ?1M is linked to a heterogeneous yellow-brown chromophore of unknown structure, and interacts with several target proteins, including ?1-inhibitor-3, fibronectin, prothrombin and albumin. To date, there is little knowledge about the interaction sites between ?1M and its partners. Here, we report the crystal structure of the human ?1M. Due to the crystallization occurring in a low ionic strength solution, the unidentified chromophore with heavy electron density is observed at a hydrophobic inner tube of ?1M. In addition, two conserved surface regions of ?1M are proposed as putative protein-protein interface sites. Further study is needed to unravel the detailed information about the interaction between ?1M and its partners.

Streptococcus pneumoniae SPD0280 is a hypothetical protein that has been putatively identified as a transcriptional regulator. However, it has very low sequence identity to other well characterized transcriptional regulators. Determination of the three-dimensional structure may provide information for the characterization of proteins; therefore, it was decided to use X-ray diffraction analysis to learn more about this protein. Here, the expression, purification, crystallization and preliminary crystallographic analysis of SPD0280 from S. pneumoniae are reported. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 45.886, b = 66.785, c = 150.050?Å, and diffracted to a resolution of 2.5?Å. The crystals are likely to contain one molecule in the asymmetric unit, with a VM value of 2.06?Å(3)?Da(-1).

Exclusive enteral nutrition (EEN) is an effective and safe remission induction treatment for Crohns disease in adults. Its influence on adults health-related quality of life remains unknown. The aim of this study was to determine the effect of EEN on health-related quality of life in adults with active Crohns disease.

MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their clinical significance for hepatocellular carcinoma.

The oxidation of light alkanes that is catalyzed by heme and nonheme iron enzymes is widely proposed to involve highly reactive {Fe(V) ?O} species or {Fe(IV) ?O} ligand cation radicals. The identification of these high-valent iron species and the development of an iron-catalyzed oxidation of light alkanes under mild conditions are of vital importance. Herein, a combination of tridentate and bidentate ligands was used for the generation of highly reactive nonheme {Fe?O} species. A method that employs [Fe(III) (Me3 tacn)(Cl-acac)Cl](+) as a catalyst in the presence of oxone was developed for the oxidation of hydrocarbons, including cyclohexane, propane, and ethane (Me3 tacn=1,4,7-trimethyl-1,4,7-triazacyclononane; Cl-acac=3-chloro-acetylacetonate). The complex [Fe(III) (Tp)2 ](+) and oxone enabled stoichiometric oxidation of propane and ethane. ESI-MS, EPR and UV/Vis spectroscopy, (18) O labeling experiments, and DFT studies point to [Fe(IV) (Me3 tacn)({Cl-acac}(.+) )(O)](2+) as the catalytically active species.

Rapid urbanization has greatly altered the urban metabolism of material and energy. As a significant part of the infrastructure, urban roads are being rapidly developed worldwide. Quantitative analysis of metabolic processes on urban road systems, especially the scale, composition and spatial distribution of their stocks, could help to assess the resource appropriation and potential environmental impacts, as well as improve urban metabolism models. In this paper, an integrated model, which covered all types of roads, intersection structures and ancillary facilities, was built for calculating the material stocks of urban road systems. Based on a bottom-up method, the total stocks were disassembled into a number of stock parts rather than obtained by input-output data, which provided an approach promoting data availability and inner structure understanding. The combination with GIS enabled the model to tackle the complex structures of road networks and avoid double counting. In the case study of Beijing, the following results are shown: 1) The total stocks for the entire road system reached 159million tons, of which nearly 80% was stored in roads, and 20% in ancillary facilities. 2) Macadam was the largest stock (111million tons), while stone mastic asphalt, polyurethane plastics, and atactic polypropylene accounted for smaller components of the overall system. 3) The stock per unit area of pedestrian overcrossing was higher than that of the other stock units in the entire system, and its steel stocks reached 0.49t/m(2), which was 10 times as high as that in interchanges. 4) The high stock areas were mainly distributed in ring-shaped and radial expressways, as well as in major interchanges. 5) Expressways and arterials were excessively emphasized, while minor roads were relatively ignored. However, the variation of cross-sectional thickness in branches and neighborhood roads will have a significant impact on the scale of material stocks in the entire road system.

Nearly monodispersed yolk-type Au@Fe3O4@C nanospheres with hollow cores of 50 nm in diameter were prepared through coating Au@SiO2 nanoparticles with Fe3O4@C double layers, followed by dissolving SiO2. The cytotoxicity of the nanospheres was evaluated by MTT assay, demonstrating a high biocompatibility. The yolk-type nanospheres show a high DOX loading content of 1237 mg g(-1). The coexistence of Fe3O4 and Au also makes the nanospheres as dual probes for MR imaging with a specific relaxivity (r2*) of 384.38 mM(-1) s(-1) and optical fluorescence imaging using a near-infrared (NIR) excitation.

A number of studies have indicated that Nurr1, which belongs to a novel class of orphan nuclear receptors (the NR4A family), is important for carcinogenesis. Here we investigated expression of Nurr1 protein in benign and malignant human prostate tissues and association with clinicopathologic features using immunohistochemical techniques. Moreover, we also investigated the ability of Nurr1 to influence proliferation, migration, invasion and apoptosis of human prostate cancer cells using small interfering RNA silencing. Immunohistochemical analysis revealed that the expression of Nurr1 protein was higher in prostate cancer tissues than in benign prostate tissue (P < 0.001), levels being positively correlated with tumor T classification (P = 0.003), N classification (P = 0.017), M classification (P = 0.011) and the Gleason score (P = 0.020) of prostate cancer patients. In vitro, silencing of endogenous Nurr1 attenuated cell proliferation, migration and invasion, and induced apoptosis of prostate cancer cells. These results suggest that Nurr1 may be used as an indicator for prostate cancer progression and be useful for novel potential therapeutic strategies.

Nanoprobes with dual modal imaging of magnetic resonance imaging (MRI) and two-photon fluorescence (TPF) can serve as promising platforms for clinical diagnosis. A wide range of molecules and nanoparticles have been investigated as agents for contrast enhanced MRI and fluorescence imaging in cancer diagnosis. However, a single material with dual modal imaging of MRI and TPF is rarely reported. We found that Mn?[Co(CN)?]?@SiO? nanocubes can serve as agents for both T?- and T?-weighted MRI, and TPF imaging. The nanocubes coated with silica to form Mn?[Co(CN)?]?@SiO? core-shell nanocubes were readily internalized by cells without showing cytotoxicity. In vitro tests, the core-shell nanocubes display relatively high longitudinal (r?) and transverse (r?) relaxivities, they also manifest a remarkable T? and T? contrast effects at in-vivo imaging of internal organs in Mice. Moreover, the core-shell nanocubes could offer high-resolution cell fluorescence imaging by two-photon excitation (720?nm) or by conventional fluorescence with 403- or 488-nm excitation.

The hydration layer plays a key role in the controlled drug release of gel-forming matrix tablets. For poorly water-soluble drugs, matrix erosion is considered as the rate limiting step for drug release. However, few investigations have reported on the quantification of the relative importance of swelling and erosion in the release of poorly soluble drugs, and three-dimensional (3D) structures of the hydration layer are poorly understood. Here, we employed synchrotron radiation X-ray computed microtomography with 9-?m resolution to investigate the hydration dynamics and to quantify the relative importance of swelling and erosion on felodipine release by a statistical model. The 3D structures of the hydration layer were revealed by the reconstructed 3D rendering of tablets. Twenty-three structural parameters related to the volume, the surface area (SA), and the specific surface area (SSA) for the hydration layer and the tablet core were calculated. Three dominating parameters, including SA and SSA of the hydration layer (SA hydration layer and SSA hydration layer ) and SA of the glassy core (SA glassy core ), were identified to establish the statistical model. The significance order of independent variables was SA hydration layer > SSA hydration layer > SA glassy core , which quantitatively indicated that the release of felodipine was dominated by a combination of erosion and swelling. The 3D reconstruction and structural parameter calculation methods in our study, which are not available from conventional methods, are efficient tools to quantify the relative importance of swelling and erosion in the controlled release of poorly soluble drugs from a structural point of view.

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